A Study of the Safety and Efficacy of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects

NCT00532779 | Completed Phase 3 Results DMC

• 2 other identifiers: NB-301COR-I
• Study Type: interventional
• Target: 1,742
• Locations: 1 country
• Sites: 34

Brief Summary

The purpose of this study is to determine whether 2 doses of the combination of naltrexone SR and bupropion SR are safe and effective in the treatment of obesity.

Conditions

Obesity; Overweight

Keywords

Obesity; Antiobesity agents; Antiobesity drugs; Overweight drug therapy; Obese drug therapy; Weight loss drug effects; Bupropion administration and dosage; Naltrexone administration and dosage; Double blind method; Combination drug therapy; Delayed action preparations

Outcome Measures

Primary Outcomes (2)

• Co-primary: Body Weight- Mean Percent Change

  Baseline, 56 weeks

• Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease

  Baseline, 56 weeks

Secondary Outcomes (16)

• Body Weight- Proportion of Subjects With ≥10% Decrease

  Baseline, 56 weeks

• Change in Waist Circumference

  Baseline, 56 weeks

• Change in Fasting HDL Cholesterol Levels

  Baseline, 56 weeks

• Change in Fasting Triglycerides Levels, Using Log-transformed Data

  Baseline, 56 weeks

• Change in IWQOL-Lite Total Scores

  Baseline, 56 weeks

Study Arms (3)

NB16

EXPERIMENTAL

Naltrexone SR 16 mg/Bupropion SR 360 mg /day with ancillary therapy

Drug: Naltrexone SR 16 mg/Bupropion SR 360 mg /day; Behavioral: Ancillary therapy

NB32

EXPERIMENTAL

Naltrexone SR 32 mg/Bupropion SR 360 mg /day with ancillary therapy

Drug: Naltrexone SR 32 mg/Bupropion SR 360 mg /day; Behavioral: Ancillary therapy

Placebo

PLACEBO COMPARATOR

Placebo with ancillary therapy

Drug: Placebo; Behavioral: Ancillary therapy

Interventions

Naltrexone SR 16 mg/Bupropion SR 360 mg /day DRUG

Also known as: NB16

NB16

Naltrexone SR 32 mg/Bupropion SR 360 mg /day DRUG

Also known as: NB32

NB32

Placebo DRUG

Placebo

Ancillary therapy BEHAVIORAL

Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

NB16; NB32; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male subjects, 18 to 65 years of age;
• Have BMI ≥30 and ≤45kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia;
• Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine; medical regimen must be stable for at least 6 weeks prior to randomization;
• Medications for treatment of dyslipidemia are allowed as long as medical regimen has been stable for at least 6 weeks prior to randomization;
• Free of opioid medication for 7 days prior to randomization;
• No clinically significant abnormality of serum albumin, blood urea nitrogen, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal range (ULN);
• No clinically significant abnormality of hematocrit, white blood cell (WBC) count, white cell differential, or platelets;
• Fasting glucose \< 126 mg/dL on no hypoglycemic agents, fasting triglycerides \<400 mg/dL;
• No clinically significant abnormality on urinalysis;
• TSH within normal limits or normal T3, if TSH is below normal limits;
• Negative serum pregnancy test in women of child-bearing potential;
• Negative urine drug screen;
• IDS-SR scores \< 2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality), and IDS-SR total score \< 30;
• Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug;

You may not qualify if:

• Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome);
• Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke);
• History of malignancy within the previous 5 years with exception of non-melanoma skin cancer or surgically cured cervical cancer;
• A lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa;
• Current serious psychiatric illness including severe personality disorder, (e.g. borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation, or recent hospitalization due to psychiatric illness;
• A response to bipolar disorder questions indicating the presence of bipolar disorder;
• In need of medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization;
• History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study initiation;
• Type 1 or Type 2 diabetes mellitus;
• Screening ECG with a corrected QT interval by the method of Bazett (QTcB) \>450 msec (men) and \> 470 millisecond (msec) (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities;
• Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents or agents for the treatment of Attention Deficit Disorder) with the exception of low dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over-the-counter dietary supplements or herbs with psychoactive, appetite or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine, cholestypol, Depo Provera®; smoking cessation agents; use of opioid or opioid-like medications, including analgesics and antitussives;
• History of surgical or device (e.g., gastric banding) intervention for obesity;
• History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures);
• History of treatment with bupropion or naltrexone within the preceding 12 months;
• History of hypersensitivity or intolerance to bupropion or naltrexone;

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (34)

Radiant Research

Birmingham, Alabama, 35209, United States

Location

SelfCenter, PC

Fairhope, Alabama, 36532, United States

Location

Radiant Research, Phoenix Southeast

Chandler, Arizona, 85225, United States

Location

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Advance Clinical Research Institute

Orange, California, 92869, United States

Location

Scripps Clinic Del Mar

San Diego, California, 92130, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

University Clinical Research

Pembroke Pines, Florida, 33024, United States

Location

Georgia Clinical Research

Atlanta, Georgia, 30308, United States

Location

CSRA Partners in Health, Inc

Augusta, Georgia, 30909, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Radiant Research

Chicago, Illinois, 60610, United States

Location

Welborn Clinic

Evansville, Indiana, 47713, United States

Location

Radiant Research Kansas City

Overland Park, Kansas, 66202, United States

Location

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, 40509, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Medical Research Institute

Slidell, Louisiana, 70458, United States

Location

Health Trends Research, LLC

Baltimore, Maryland, 21209, United States

Location

FutureCare Studies

Springfield, Massachusetts, 01103, United States

Location

Center for Nutrition and Metabolic Disorders

Reno, Nevada, 89557, United States

Location

Center for Nutrition and Preventive Medicine

Charlotte, North Carolina, 28211, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, 27612, United States

Location

Rapid Medical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Central Ohio Nutrition Center, Inc.

Columbus, Ohio, 43213, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Summit Research Network (Oregon), Inc.

Portland, Oregon, 97210, United States

Location

Internal Medicine Associates of Cordova

Cordova, Tennessee, 38018, United States

Location

Jackson Clinic, PA

Jackson, Tennessee, 38305, United States

Location

Covance Clinical Research Unit Austin

Austin, Texas, 78752, United States

Location

Radiant Research

Dallas, Texas, 75231, United States

Location

Baylor Endocrine Center

Dallas, Texas, 75246, United States

Location

Radiant Research

San Antonio, Texas, 78217, United States

Location

Oakwell Clinical Research

San Antonio, Texas, 78218, United States

Location

Related Publications (1)

• Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. doi: 10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29.

  PMID: 20673995 RESULT

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Head of Global Development
• Organization: Orexigen Therapeutics, Inc.

MedInfo@Orexigen.com

(858) 875-8600

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2007
• First Posted: September 20, 2007
• Study Start: October 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: November 21, 2014
• Results First Posted: November 21, 2014

Record last verified: 2014-11

Locations

US (34)